Ciproxin 750mg Film-coated Tablets

The Summary of Product Characteristics (SPC or SmPC) is a specific document, the wording of which has been agreed with the regulatory authority as part of the medicine approval process. It is required before any medicine is allowed on the market in Europe. It is designed to assist doctors and pharmacists in prescribing and supplying the product.

In clinical studies, it was demonstrated that fluvoxamine, as a strong inhibitor of the CYP450 1A2

isoenzyme, markedly inhibits the metabolism of agomelatine resulting in a 60-fold increase of

agomelatine exposure. Although no clinical data are available for a possible interaction with ciprofloxacin, a moderate inhibitor of CYP450 1A2, similar effects can be expected upon concomitant administration (see ‘Cytochrome P450’ in section 4.4).

Zolpidem

Co-administration of ciprofloxacin may increase blood levels of zolpidem, concurrent use is not

recommended.

Section 4.8 - was amended as follows:

- Antibiotic associated colitis deleted under SOC “Infections and Infestations” and moved to SOC

“Gastrointestinal disorders”

-Addition of mania/hypomania

- Addition of DRESS to ADR list

-“arthralgia” and “arthritis” in brackets after the term “arthropathy”

Updated on 9 June 2016 SmPC

Reasons for updating

New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 18 November 2015 SmPC

Reasons for updating

Change to section 4.4 - Special warnings and precautions for use

Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

﻿

In section
4.4 Special warnings and precautions for use, the following section has been
added:

Vision
disorders

If vision becomes impaired or any effects on the eyes
are experienced, an eye specialist should be consulted immediately.

In section 4.8, the following text has been added:

Reporting
of suspected adverse reactions

Reporting
suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the
medicinal product. Healthcare professionals are asked to report any suspected
adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin
2; Tel: +353 1 6764971;Fax: +353 1
6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie. By reporting side
effects you can help provide more information on the safety of this medicine.

Updated on 18 November 2015 PIL

Reasons for updating

Change to warnings or special precautions for use

Addition of information on reporting a side effect.

Updated on 2 January 2014 SmPC

Reasons for updating

Change to Section 4.8 – Undesirable effects - how to report a side effect

Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the online reporting option (preferred method) accessible from the IMB homepage (www.imb.ie). A downloadable report form is also accessible from the IMB website, which may be completed manually and submitted to the IMB via ‘freepost’ (see details below). Alternatively, the traditional post-paid ‘yellow card’ option may also be used.

Inhalation anthrax post-exposure prophylaxis and curative treatment for persons able to receive treatment by oral route when clinically appropriate. Drug administration should begin as soon as possible after suspected or confirmed exposure.

Resistance to fluoroquinolones of Escherichia coli – the most common pathogen involved in urinary tract infections – varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in Escherichia coli to fluoroquinolones.

The single dose of ciprofloxacin, that may be used in uncomplicated cystitis in pre-menopausal women, is expected to be associated with lower efficacy than with the longer treatment duration. This is all the more to be taken into account as regards the increasing resistance level of Escherichia coli to quinolones.

Paediatric populationChildren and adolescents

The use of ciprofloxacin in children and adolescents should follow available official guidance. Ciprofloxacin treatment should be initiated only by physicians who are experienced in the treatment of cystic fibrosis and/or severe infections in children and adolescents.

Musculoskeletal System

Ciprofloxacin should be used with caution in patients with myasthenia gravis, because symptoms can be exacerbated (see section 4.8).

Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including ciprofloxacin, in these populations.

As with other quinolones, hypoglycemia has been reported most often in diabetic patients, predominantly in the elderly population. In all diabetic patients, careful monitoring of blood glucose is recommended (see section 4.8).

4.5Interaction with other medicinal products and other forms of interaction

Chelation Complex Formation

The simultaneous administration of ciprofloxacin (oral) and multivalent cation-containing drugs and mineral supplements (e.g. calcium, magnesium, aluminium, iron), polymeric phosphate binders (e.g. sevelamer or lanthanum carbonate), sucralfate or antacids, and highly buffered drugs (e.g. didanosine tablets) containing magnesium, aluminium, or calcium reduces the absorption of ciprofloxacin. Consequently, ciprofloxacin should be administered either 1‑2 hours before or at least 4 hours after these preparations. The restriction does not apply to antacids belonging to the class of H2 receptor blockers

Glibenclamide

In particular cases, concurrent administration of ciprofloxacin and glibenclamide containing medicinal products can intensify the action of glibenclamide (hypoglycaemia).

4.6Pregnancy and lactation

Breast-feedingLactation

Ciprofloxacin is excreted in breast milk. Due to the potential risk of articular damage, ciprofloxacin should not be used during breast-feeding.

4.8Undesirable effects

The most commonly reported adverse drug reactions (ADRs) are nausea and diarrhoea.

ADRs derived from clinical studies and post-marketing surveillance with Ciproxin (oral, intravenous, and sequential therapy) sorted by categories of frequency are listed below. The frequency analysis takes into account data from both oral and intravenous administration of ciprofloxacin.

The incidence of arthropathy, mentioned above, is referring to data collected in studies with adults. In children, arthropathy is reported to occur commonly (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to the Irish Medicines Board (online at www.imb.ie, telephone 01-6764971 or using the yellow card system).

[*For the printed material, please refer to the guidance of the annotated QRD template.]

5.PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacokinetic/pharmacodynamicPK/PD relationship:

Efficacy mainly depends on the relation between the maximum concentration in serum (Cmax) and the minimum inhibitory concentration (MIC) of ciprofloxacin for a bacterial pathogen and the relation between the area under the curve (AUC) and the MIC.

5.2Pharmacokinetic properties

BiotransformationMetabolism

Low concentrations of four metabolites have been reported, which were identified as: desethyleneciprofloxacin (M 1), sulphociprofloxacin (M 2), oxociprofloxacin (M 3) and formylciprofloxacin (M 4). The metabolites display in-vitro antimicrobial activity but to a lower degree than the parent compound.

10.DATE OF REVISION OF THE TEXT

November 2012September 2013

Updated on 1 October 2013 PIL

Reasons for updating

Change to warnings or special precautions for use

Change of contraindications

Change to side-effects

Change to drug interactions

Change to information about pregnancy or lactation

Change to date of revision

Change to improve clarity and readability

Addition of information on reporting a side effect.

Updated on 7 January 2013 SmPC

Reasons for updating

Change to section 4.1 - Therapeutic indications

Change to section 4.2 - Posology and method of administration

Change to section 4.4 - Special warnings and precautions for use

Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Change to section 4.8 - Undesirable effects

Change to section 4.9 - Overdose

Change to section 5.1 - Pharmacodynamic properties

Change to section 9 - Date of renewal of authorisation

Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Red text = text removed

Blue text = text added
in

Section
4.1 Therapeutic indications

·Gonococcal uretritis and cervicitis

·Epididymo-orchitis including cases due to Neisseria gonorrhoeae

·Pelvic inflammatory disease including cases due to Neisseria gonorrhoeae

In the above genital tract infections when thought or known to be due to Neisseria gonorrhoeae
it is particularly important to obtain local information on the prevalence of
resistance to ciprofloxacin and to confirm susceptibility based on laboratory
testing.

·Genital tract infections

·gonococcal uretritis and cervicitis due to susceptible Neisseria
gonorrhoeae

·epididymo-orchitis
including cases due to susceptible Neisseria gonorrhoeae

·pelvic
inflammatory disease including cases due to susceptible Neisseria
gonorrhoeae

Ciprofloxacin may be used in
the management of neutropenic patients with fever that is suspected to be due
to a bacterial infection.

Section 4.2 Posology and method of administration

………………………………………………….

Indications

Daily
dose in mg

Total duration of treatment (potentially including
initial parenteral treatment with ciprofloxacin

Urinary tract infections

(see section 4.4)

Uncomplicated
cystitis

250 mg twice daily to 500 mg twice daily

3 days

Complicated
cystitis, Uncomplicated pyelonephritis

In pre-menopausal women, 500 mg single dose may be used

Complicated
pyelonephritis

500 mg twice daily

7 days

Prostatitis

500 mg twice daily to 750 mg twice daily

2
to 4 weeks (acute) to 4 to 6 weeks (chronic)

…………………………………………………..

Indications

Daily
dose in mg

Total duration of treatment (potentially including
initial parenteral treatment with ciprofloxacin

Treatment of
infections or prophylaxis of infections in neutropenic patients

Neutropenic patients with fever that is suspected to be due to a
bacterial infection.

Ciprofloxacin should be
co-administered with appropriate antibacterial agent(s) in accordance to
official guidance.

500 mg
twice daily to 750 mg twice daily

Therapy
should be continued over the entire period of neutropenia

…………………………………………………..

Section 4.4 Special warnings and precautions for use

…………………………………………………..

Genital tract
infections

Epididymo-orchitis and
pelvic inflammatory diseases may be caused by fluoroquinolone-resistant Neisseria
gonorrhoeae. Ciprofloxacin should be co-administered with another
appropriate antibacterial agent unless ciprofloxacin-resistant Neisseria
gonorrhoeae can be excluded. If clinical improvement is not achieved after
3 days of treatment, the therapy should be reconsidered.

Therefore, ciprofloxacin
should be administered for the treatment of gonococcal uretritis or cervicitis
only if ciprofloxacin-resistant Neisseria gonorrhoeae can be excluded.

For epididymo-orchitis and
pelvic inflammatory diseases, empirical ciprofloxacin should only be considered
in combination with another appropriate antibacterial agent (e.g. a
cephalosporin) unless ciprofloxacin-resistant Neisseria gonorrhoeae can
be excluded. If clinical improvement is not achieved after 3 days of treatment,
the therapy should be reconsidered.

Urinary tract infections

Resistance to fluoroquinolones of Escherichia
coli – the most common pathogen
involved in urinary tract infections – varies across the European Union.
Prescribers are advised to take into account the local prevalence of resistance
in Escherichia coli to fluoroquinolones.

The single dose of ciprofloxacin is expected to be
associated with lower efficacy than with the longer treatment duration. This is
all the more to be taken into account as regards the increasing resistance
level of Escherichia coli to quinolones.

…………………………………………………………..

Musculoskeletal System

Ciprofloxacin should
generally not be used in patients with a history of tendon disease/disorder
related to quinolone treatment. Nevertheless, in very rare instances, after
microbiological documentation of the causative organism and evaluation of the
risk/benefit balance, ciprofloxacin may be prescribed to these patients for the
treatment of certain severe infections, particularly in the event of failure of
the standard therapy or bacterial resistance, where the microbiological data
may justify the use of ciprofloxacin.

Tendinitis and tendon
rupture (especially Achilles tendon), sometimes bilateral, may occur with
ciprofloxacin, even within as soon asthe
first 48 hours of treatment. Inflammation
and ruptures of tendon may occur even up to several months after
discontinuation of ciprofloxacin therapy. The risk of tendinopathy may
be increased in elderly patients or in patients concomitantly treated with
corticosteroids (see section 4.8).

……………………………………………………………

Central Nervous System

Ciprofloxacin
like otherQuinolonesquinolones are known to trigger seizures or lower the
seizure threshold. Cases of
status epilepticus have been reported. Ciprofloxacin
should be used with caution in patients with CNS disorders which may be
predisposed to seizure. If seizures occur ciprofloxacin should be discontinued
(see section 4.8). Psychiatric reactions may occur even after thefirst
administration of ciprofloxacin. In rare cases, depression or psychosis can
progress to suicidal
ideations/thoughts culminating in attempted suicide or completed suicide self endangering behaviour. In the occurrence of suchthesecases,
ciprofloxacin should be discontinued.

Cases of polyneuropathy (based on neurological
symptoms such as pain, burning, sensory disturbances or muscle weakness, alone
or in combination) have been reported in patients receiving ciprofloxacin.
Ciprofloxacin should be discontinued in patients experiencing symptoms of
neuropathy, including pain, burning, tingling, numbness, and/or weakness in
order to prevent the development of an irreversible condition (see section
4.8).

Cardiac disorders

Since
ciprofloxacin is associated with cases of QT prolongation (see section 4.8),
caution should be exercised when treating patients at risk for torsades de
pointes arrhythmia.

Caution should be
taken when using fluoroquinolones, including ciprofloxacin, in patients with
known risk factors for prolongation of the QT interval such as, for example:

·congenital long QT syndrome

·concomitant use of drugs that are known to prolong the
QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic
antidepressants, macrolides, antipsychotics)

Since ciprofloxacin is
largely excreted unchanged via renal pathway dose adjustment is needed in
patients with impaired renal function as described in section 4.2 to avoid an
increase in adverse drug reactions due to
accumulation of ciprofloxacin.

…………………………………………………………..

Cytochrome P450

Ciprofloxacin inhibits CYP1A2 and thus may cause
increased serum concentration of concomitantly administered substances
metabolised by this enzyme (e.g. theophylline, clozapine, olanzapine, ropinirole, tizanidine, duloxetine).
Co-administration of ciprofloxacin and tizanidine is contra-indicated.
Therefore, patients taking these substances concomitantly with ciprofloxacin
should be monitored closely for clinical signs of overdose, and determination
of serum concentrations (e.g. of theophylline) may be necessary (see section
4.5).

………………………………………………….

Section 4.5 Interaction with other medicinal products
and other forms of interactions

Effects of other products on
ciprofloxacin:

Drugs known to prolong QT interval

Ciprofloxacin, like other fluoroquinolones, should be used
with caution in patients receiving drugs known to prolong QT interval (e.g.
Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides,
antipsychotics) (see section 4.4).

…………………………………………..

Metoclopramide

Metoclopramide accelerates the absorption of ciprofloxacin (oral)
resulting in a shorter time to reach maximum plasma concentrations. No effect
was seen on the bioavailability of ciprofloxacin.

Omeprazole

Concomitant administration of ciprofloxacin and omeprazole containing
medicinal products results in a slight reduction of Cmax and AUC of
ciprofloxacin.

………………………………………………..

Cyclosporin

A transient rise in the concentration of serum creatinine was observed
when ciprofloxacin and cyclosporin containing medicinal products were
administered simultaneously. Therefore, it is frequently (twice a week)
necessary to control the serum creatinine concentrations in these patients.

Vitamin K
antagonists Oral
Anticoagulants

Simultaneous administration of
ciprofloxacin with warfarin
a vitamin K antagonist may augment its anti-coagulant effects. There have been many reports of increases in oral anticoagulant activity
in patients receiving antibacterial agents, including fluoroquinolones. The
risk may vary with the underlying infection, age and general status of the
patient so that the contribution of the fluroquinoloneciprofloxacin to the increase in INR
(international normalised ratio) is difficult to assess. It is recommended thatThe INR should be monitored
frequently during and shortly after co-administration of ciprofloxacin with an oral anticoagulant
agent a vitamin K antagonist (e.g.,
warfarin, acenocoumarol, phenprocoumon, or fluindione).

Glibenclamide

In particular cases, concurrent administration of ciprofloxacin and
glibenclamide containing medicinal products can intensify the action of
glibenclamide (hypoglycaemia).

Duloxetine

In clinical studies, it was demonstrated that concomitant use of
duloxetine with strong inhibitors of the CYP450 1A2 isozyme such as
fluvoxamine, may result in an increase of AUC and Cmax of duloxetine. Although
no clinical data are available on a possible interaction with ciprofloxacin,
similar effects can be expected upon concomitant administration (see section
4.4).

………………………………………..

Lidocaine

It was demonstrated in
healthy subjects that concomitant use of lidocaine containing medicinal
products with ciprofloxacin, a moderate inhibitor of CYP450 1A2 isozyme,
reduces clearance of intravenous lidocaine by 22%. Although lidocaine treatment
was well tolerated, a possible interaction with ciprofloxacin associated with
side effects may occur upon concomitant administration.

………………………………………….

Sildenafil

Cmax and AUC of sildenafil were increased approximately
twofold in healthy subjects after an oral dose of 50 mg given concomitantly
with 500 mg ciprofloxacin. Therefore, caution should be used prescribing
ciprofloxacin concomitantly with sildenafil taking into consideration the risks
and the benefits.

*These events were reported during the
postmarketing period and were observed predominantly among patients with
further risk factors for QT prolongation (see section 4.4).

Section 4.9 Overdose

…………………………

Apart from routine emergency
measures, e.g. ventricular
emptying followed by medical carbon, it is recommended to monitor renal
function, including urinary pH and acidify, if required, to prevent
crystalluria. Patients should be kept well hydrated. Calcium or magnesium containing antacids may
theoretically reduce the absorption of ciprofloxacin in overdoses.

Only a small quantity of
ciprofloxacin (<10%) is eliminated by haemodialysis or peritoneal dialysis.

In the
event of overdose, symptomatic treatment should be implemented. ECG monitoring
should be undertaken, because of the possibility of QT interval prolongation.

*Non-species-related breakpoints have been
determined mainly on the basis of PK/PD data and are independent of MIC
distributions of specific species. They are for use only for species that
have not been given a species-specific breakpoint and not for those species
where susceptibility testing is not recommended.

9.DATE OF FIRST
AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first
authorisation: 20th December 1988

Date of last renewal: 20th December 20089th
October 2010

Section 10. Date of Revision of the text

September 2010

November 2012

Updated on 21 December 2012 PIL

Reasons for updating

Change to warnings or special precautions for use

Change to side-effects

Change to drug interactions

Change to further information section

Change to date of revision

Change to improve clarity and readability

Updated on 23 January 2012 PIL

Reasons for updating

Change to further information section

Change to date of revision

Updated on 17 November 2010 SmPC

Reasons for updating

Change to section 2 - Qualitative and quantitative composition

Change to section 3 - Pharmaceutical form

Change to section 6.1 - List of excipients

Change to section 6.4 - Special precautions for storage

Change to section 6.5 - Nature and contents of container

Change to section 6.6 - Special precautions for disposal and other handling

Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)